Neuromedin U (Nmu) is an evolutionarily conserved neuropeptide. It regulates diverse physiological effects such as blood pressure, stress and allergic responses, metabolic and feeding behavior, pain perception, and neuroendocrine functions [3]. It signals via two G-protein-coupled receptors, NMUR1 and NMUR2, and is involved in pathways related to energy homeostasis, circadian rhythm regulation, and bone remodeling [1,2,3]. Genetic models like knockout mice are valuable for studying Nmu's functions.

Global loss of Nmu expression in male and female mice leads to high bone mass due to elevated bone formation rate, suggesting Nmu negatively regulates osteoblast differentiation [3,5]. Nmu/Nms/Gpr176 triple-deficient mice show enhanced light-resetting of circadian locomotor activity, indicating a role of Nmu in modulating light-induced phase shift in the circadian clock [2]. In cancer, high expression of Nmu is associated with poor prognosis in lung adenocarcinoma, colon cancer, and endometrial cancer [4,6,7].

In summary, Nmu is crucial for multiple biological processes. Gene knockout mouse models have revealed its role in bone remodeling, circadian rhythm modulation, and cancer progression. Understanding Nmu's functions provides potential targets for treating metabolic disorders, circadian rhythm-related problems, and certain cancers [1,2,4,6,7].

References:

1. Malendowicz, Ludwik K, Rucinski, Marcin. 2021. Neuromedins NMU and NMS: An Updated Overview of Their Functions. In Frontiers in endocrinology, 12, 713961. doi:10.3389/fendo.2021.713961. https://pubmed.ncbi.nlm.nih.gov/34276571/

2. Yamaguchi, Yoshiaki, Murai, Iori, Takeda, Momoko, Miyake, Takahito, Doi, Masao. . Nmu/Nms/Gpr176 Triple-Deficient Mice Show Enhanced Light-Resetting of Circadian Locomotor Activity. In Biological & pharmaceutical bulletin, 45, 1172-1179. doi:10.1248/bpb.b22-00260. https://pubmed.ncbi.nlm.nih.gov/35908898/

3. Hsiao, Yu-Tin, Manikowski, Kelli J, Snyder, Samantha, Allen, Matthew R, Lowery, Jonathan W. 2021. NMUR1 in the NMU-Mediated Regulation of Bone Remodeling. In Life (Basel, Switzerland), 11, . doi:10.3390/life11101028. https://pubmed.ncbi.nlm.nih.gov/34685399/

4. Tang, Yan, Hu, Chunsheng. 2021. NMU Is a Poor Prognostic Biomarker in Patients with Lung Adenocarcinoma. In Disease markers, 2021, 5031479. doi:10.1155/2021/5031479. https://pubmed.ncbi.nlm.nih.gov/34336003/

5. Hsiao, Yu-Tin, Jestes, Kelli J, Jackson, Krista L, Hum, Julia M, Lowery, Jonathan W. 2020. Neuromedin U (NMU) regulates osteoblast differentiation and activity. In Biochemical and biophysical research communications, 524, 890-894. doi:10.1016/j.bbrc.2020.02.003. https://pubmed.ncbi.nlm.nih.gov/32057362/

6. Chen, Danyu, Ye, Zhen, Lew, Zhenxian, Yu, Zhong, Lin, Ying. . Expression of NMU, PPBP and GNG4 in colon cancer and their influences on prognosis. In Translational cancer research, 11, 3572-3583. doi:10.21037/tcr-22-1377. https://pubmed.ncbi.nlm.nih.gov/36388046/

7. Lin, Ting-Yu, Wu, Fang-Ju, Chang, Chia-Lin, Li, Zhongyou, Luo, Ching-Wei. . NMU signaling promotes endometrial cancer cell progression by modulating adhesion signaling. In Oncotarget, 7, 10228-42. doi:10.18632/oncotarget.7169. https://pubmed.ncbi.nlm.nih.gov/26849234/